Cardiac Cell Therapy 3.0
The Beginning of the End or the End of the Beginning?
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- cardiac precursors
- cardiovascular diseases
- cell- and tissue-based therapy
- endothelial progenitor cells
- mesenchymal stromal cells
Cardiac cell therapy (CCT) holds great promise as a regenerative medicine approach for the treatment of cardiovascular diseases (CVDs).1 The first generation of CCTs tested various adult cell types, including skeletal myoblasts, bone marrow (BM)–derived mesenchymal stem cells (MSCs), and cardiac progenitor cells (CPCs). More recently, the advent of induced pluripotent stem cells (PSCs) led to the much-anticipated second generation of CCTs with bona fide, PSC-derived CPCs and cardiomyocytes.1 The bad news is that, to date, both adult and PSC-based CCTs have failed to meet their promise of directly remuscularizing and repairing the heart to a therapeutically meaningful extent.2,3 The good news is that some cell types clearly demonstrate encouraging results in terms of efficacy and safety and, more importantly, reveal a previously underestimated key role of CCT, to indirectly promote repair by regulating mechanisms of endogenous cardiac regeneration in the host.1,4
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The increasingly high burden of CVDs, coupled with the limited efficacy seen in both adult and PSC-based CCTs, and incomplete mechanistic understanding of adult human heart regeneration, have fueled disappointment, skepticism, and polarized the field.5 This schism has been particularly apparent in the area of adult CCTs, which also faces a current crisis of scientific distrust.5 However, the interpretation that a possible stumble in research progress is proof that CCT is broken would be unscientific. As Daniel Wegner noted, “…tipping the balance toward skepticism can eradicate ideas faster than we can generate them. Eventually, we arrive at a vacuous chasm, with no theory standing and no idea left without serious wounds.”6
Under this prism, it is worth exploring how the field of adult CCTs fares, compared with other regenerative medicine approaches. PSC-based CCTs offer perhaps the …